{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:52:35Z","timestamp":1792641155099,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>There are limited conventional chemotherapy options for biliary tract cancers (BTCs), a heterogenous group of lethal, rare malignancies. The receptor tyrosine kinase (RTK) is closely associated with the progression of human malignancies through the regulation of cell cycle. Overexpression or amplification of RTKs has been investigated as a potential biomarker and therapeutic target in BTC; herein, we investigate the value of such interventions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Materials and Methods<\/jats:title>\n                  <jats:p>Overexpression of RTK proteins was examined by immunohistochemistry in 193 BTC samples, of which 137 were gallbladder carcinoma, 29 were perihilar cholangiocarcinoma, and 27 were intrahepatic cholangiocarcinoma. Silver in situ hybridization of MET and HER2 was performed to assess gene amplification.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the entire cancer group, gallbladder, perihilar, and intrahepatic, MET amplification rates were 15.7%, 19.0%, 3.4%, and 14.8%, respectively, and of HER2 amplification rates were 22.4%, 27.2%, 17.2%, and 3.7%, respectively. MET and HER2 protein expressions were significantly correlated with their gene amplification status. RTKs were significantly associated with adverse clinicopathologic features such as advanced pT category and lymph node metastasis. Overall survival was significantly shorter in MET-amplified (P\u2005=\u2005.024) and EGFR-overexpressed cases (P\u2005=\u2005.045). Recurrence-free survival was significantly correlated with HER2-amplified (P\u2005=\u2005.038) and EGFR-overexpressed cases (P\u2005=\u2005.046) in all patient groups. Overall and recurrence-free survival were significantly shorter in patients who were double positive for HER2 and EGFR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae076","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T18:47:33Z","timestamp":1715021253000},"page":"e1051-e1060","source":"Crossref","is-referenced-by-count":32,"title":["EGFR, HER2, and MET gene amplification and protein expression profiles in biliary tract cancer and their prognostic significance"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-884X","authenticated-orcid":false,"given":"Yeseul","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Korea College of Medicine, Anam Hospital , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seungyun","family":"Jee","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Asan Medical Center, University of Ulsan College of Medicine , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunsung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Hanyang University , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Sam","family":"Paik","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Hanyang University , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine, Hanyang University , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Hyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pathology, National Police Hospital , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9114-8438","authenticated-orcid":false,"given":"Su-Jin","family":"Shin","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine , Seoul , Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"issue":"Suppl 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